BCG lowers plasma cholesterol levels and delays atherosclerotic lesion progression in mice

Abstract

BCG reduces plasma nonHDL-cholesterol levels and delays atherosclerotic lesion formation in hyperlipidemic mice.

Epigenetics and Trained Immunity

“…Vaccination with BCG accelerates atherosclerosis in rabbits fed a cholesterol-rich diet (69). In contrast, other studies have reported a protective effect in atherosclerosis-prone mice (100,131), which might be due to its cholesterol-lowering action. Perhaps most compelling are recent observations that nonmicrobial products, including lipoproteins that are known drivers of cardiovascular disease, can also induce trained immunity (Table 1).…”

Trained Immunity: An Underlying Driver of Inflammatory Atherosclerosis

“…In line with this, a recent genome-wide H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) analysis showed that the gene encoding receptor of oxLDL which is a marker of atherosclerosis, as well as genes directly related to inflammation, are enriched with H3K27ac in monocytes upon BCG vaccination (22), indicating that these pro-atherogenic genes are primed for an activation state in BCG-trained monocytes which could in turn contribute to atherosclerosis. However, it is noteworthy that several additional studies showed opposite results, pointing toward a beneficial effect of BCG vaccination on ASCVD (56)(57)(58). For example, in a human epidemiological cohort study, children vaccinated with BCG only showed a hazard ratio of 0.36 to develop cardiovascular diseases (58).…”

Monocyte and macrophage immunometabolism in atherosclerosis

“…However, other data suggest that hyperlipidemic mice fed a high-cholesterol diet had a delayed atherosclerotic plaque formation 6 weeks following BCG injection. It is important to realize, though, that in these mice, the BCG administration significantly lowered non-HDL cholesterol levels [ 15 ].…”